Friday, August 28, 2015

Foxp3+ T cell deficiency leads to lethal immunopathology in mice and severe organ pathology in humans (IPEX syndrome). Over the past 20 years numerous mechanisms of action of Foxp3+ T cells have been described. In fact, this number is so numerous that it wouldn't be a "heresy" from my part to claim that no single Foxp3+ T cell phenotype could explain it. This leaves us with the hypothesis that multiple versions of Foxp3+ T cells exist, each of them using selective path for immune regulation and suppression.

In summary, these data tend to reinforce the idea that Foxp3+ T cells could function in a tissue selective manner and are most likely controlled by tissue environment as suggested by Polly Matzinger and Tirumalai Kamala. This could explain why there are so mechanisms of suppression by Tregs, at least one mechanism for each tissue.

What are some of the weaknesses of this study? First, injection of amphiregulin to hosts with Foxp3+ T cell-specific deletion of amphiregulin would have been useful. Second, data regarding IL-18Rdeficient Foxp3+ T cells could have provided in vivo confirmation for this study (the authors simply mentioned that they have done experiments with bone marrow chimera to test the role of IL-18R in amphiregulin up-regulation and that it supported their conclusions).

Why is this study important? Because without our mastery of Foxp3+ T cell biology we will not be able to make any major, predictable advances in treating human immune related conditions (cancer, allergy, autoimmune conditions).